Search

Background: Evaluating organ suitability for transplantation based on infection risk is a core competency in transplant infectious disease (TID). It is unclear if trainees have opportunities to practice during training. We created a simulation curriculum to develop and evaluate this skill among infectious disease (ID) trainees. Methods: We created six simulation questions about organ suitability for transplant based on infection risk. During trainees' TID rotations, faculty texted or paged the simulation cases posing as the transplant coordinator. Trainees had 15 min to ask questions before deciding the suitability of the organ and explained their clinical reasoning in a survey. Trainees completed a post‐simulation survey to evaluate its effectiveness. Results: ID trainees, including residents and fellows on rotation, from seven centers participated. Eighty‐seven percent (13/15) of trainees felt the simulation was effective in teaching them this concept, and 80% (12/15) felt prepared for clinical practice. The proportion of correct responses was generally high among the six different cases (43%–100%); correct responses increased for some cases in the post‐activity survey. Of the 100 clinical reasoning decisions made during the activity, 19% were discordant, where the trainee correctly identified suitable organs for incorrect reasons. Conclusion: Our simulation was effective in teaching when to accept or reject an organ for transplant and was a valuable educational tool. By evaluating clinical reasoning for decisions our simulation provides educators with nuanced insight and allows for targeted coaching. This study demonstrates a critical need for further educational tools in TID. [ABSTRACT FROM AUTHOR]

Background: The use of vaccination to prevent infection has a long history, starting in the 1700s with Jenner. New innovations have led to improvements in the safety and efficacy of vaccines, from live attenuated viruses to subunit vaccines, to RNA‐based vaccination for SARS‐CoV‐2. Despite this progress, however, solid organ transplant (SOT) recipients on immunosuppression demonstrate an impaired vaccine response compared with healthy controls. This issue is important given the increased vulnerability to infection in immunocompromised patients, especially in the setting of the Coronavirus Disease 2019 (COVID‐19) pandemic. Methods: We reviewed the literature on key topics in vaccination with significant clinical impact on SOT patients. Results: Prior to COVID‐19, a large amount of data has been published demonstrating impaired humoral and T‐cell responses to multiple vaccinations targeting influenza, hepatitis B, VZV, and Pneumococcus. Poor immunogenicity can be addressed through the use of adjuvants to boost the immune response, even in the setting of senescence related to age or immunosuppression. New vaccines provide hope for preventing infection due to hepatitis C and Cytomegalovirus, and to the emerging infection, monkeypox. The data on the impact of the COVID‐19 vaccine in SOT patients is reviewed, with a focus on seroconversion, antibody titer, and antigen‐specific T cells. Factors associated with impaired response, including mycophenolate, are described. Conclusion: The history of vaccination demonstrates how scientific breakthroughs can be applied to clinical challenges. New approaches using adjuvants, strategic antigen selection, and RNA‐based vaccines offer the potential to improve immune response in SOT recipients. Future innovations are needed to better protect the vulnerable immunocompromised host. [ABSTRACT FROM AUTHOR]

Hence, low-level CMV viremia during letermovir prophylaxis may enable HCT recipients to safely develop some degree of CMV cell-mediated immunity (CMV-CMI) and prevent clinically significant CMV disease (csCMV) after completion of prophylaxis. They measured CMV-CMI in 70 CMV seropositive CBT recipients using a CMV-specific interferon-gamma/interleukin 2 (IFN- /IL-2) FLUOROSpot assay prior to transplant, and D+90, D+180 and D+360 post-transplant. Cytomegalovirus (CMV) reactivation is a leading cause of morbidity and mortality among hematopoietic cell transplant (HCT) recipients. Like watching a soccer game through a keyhole: Cytomegalovirus cell-mediated immunity incompletely reveals risk for clinically significant cytomegalovirus reactivation in cord blood transplant recipients. [Extracted from the article]

Background: The COVID‐19 pandemic has caused significant morbidity and mortality in solid organ transplant (SOT) recipients. However, it remains unclear whether the risk factor for SOT patients is the immunosuppression inherent to transplantation versus patient comorbidities. Methods: We reviewed outcomes in a cohort of SOT (n = 129) and non‐SOT (NSOT) patients (n = 708) admitted to the University of California, Los Angeles for COVID‐19 infection. Data analyses utilized multivariate logistic regression to evaluate the impact of patient demographics, comorbidities, and transplant status on outcomes. SOT patients were analyzed by kidney SOT (KSOT) versus nonkidney SOT (NKSOT) groups. Results: SOT and NSOT patients with COVID‐19 infection differed in terms of patient age, ethnicity, and comorbidities. NKSOT patients were the most likely to experience death, with a mortality rate of 16.2% compared with 1.8% for KSOT and 8.3% for NSOT patients (p =.013). Multivariable analysis of hospitalized patients revealed that patient age (odds ratio [OR] 2.79, p =.001) and neurologic condition (OR 2.66, p <.001) were significantly associated with mortality. Analysis of ICU patients revealed a 2.98‐fold increased odds of death in NKSOT compared with NSOT patients (p =.013). Conclusions: This study demonstrates the importance of transplant status in predicting adverse clinical outcomes in patients hospitalized or admitted to the ICU with COVID‐19, especially for NKSOT patients. Transplant status and comorbidities, including age, could be used to risk stratify patients with COVID‐19. This data suggests that immunosuppression contributes to COVID‐19 disease severity and mortality and may have implications for managing immunosuppression, especially for critically ill patients admitted to the ICU. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M. hominis isolates identified from SOT patients. Methods: This is a single‐center retrospective study evaluating SOT recipients with confirmed M. hominis infections. Patients' demographic, clinical, microbiological, and radiographic data were collected. Culture of M. hominis isolates was performed according to current Clinical and Laboratory Standards Institute guidelines. Phenotypic susceptibility testing was performed by University of Alabama Diagnostic Mycoplasma Laboratory. Whole genome sequencing (WGS) was performed followed by bioinformatic analysis of known genetic determinants of resistance. Results: Seven SOT recipients with M. hominis infections were identified. Two out of seven (28.5%) patients had resistance detected by phenotypic susceptibility testing (Case 5 to levofloxacin and Case 7 to tetracycline). Genomic analyses confirmed the presence of mutations in the parC and parE topoisomerase genes at positions conferring to fluoroquinolone resistance in the isolate from Case 5, while the tetracycline‐resistant isolate from Case 7 harbored the tetM gene. The median TAT from the date of specimen collection was 24 days for phenotypic susceptibility testing and 14 days for genotypic susceptibility testing. All seven patients received antimicrobials directed toward M. hominis and recovered with complete resolution of infection. Conclusions: WGS may offer a novel and more rapid methodology for M. hominis susceptibility testing to help optimize antimicrobial usage, but more data are needed. [ABSTRACT FROM AUTHOR]

Introduction: Frailty status affects outcomes after heart transplantation, but the optimal way to assess frailty prior to transplant remains unknown. Methods: This single‐center, observational study assessed 44 heart transplant candidates for frailty using three methods. The Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) were used as two physical assessments of frailty. The Frailty Risk Score (FRS) was used as a chart‐review based assessment measuring 20 different biopsychosocial and functional components, including biomarkers, depression, cognitive impairment, and sleep. Results: We determined the correlation between FRS, SPPB, and FFP and how each correlated with clinical outcomes. Of 44 participants, mean age was 60 years. FRS correlated with SPPB and FFP (P =.043, P <.001, respectively). Higher frailty as measured by SPPB and FRS was significantly associated with lack of achieving waitlist status (P =.022; P =.002) and not being transplanted (P =.026; P =.008). Higher frailty by SPPB and FFP was also associated with mortality (P =.010; P =.025). Conclusion: SPPB and chart‐review FRS showed potential for predicting waitlist and transplant status of heart transplant candidates, while SPPB and FFP were associated with mortality. Additional studies may serve to validate these observations. [ABSTRACT FROM AUTHOR]

Frailty, defined as a state of decreased physiologic reserve, has been correlated with poorer outcomes after hospitalization or surgery. Studies in lung transplant patients have associated frailty with an increased risk of post‐transplant mortality; however, a unified approach is lacking. The identification of frail patients can help clinicians pre‐emptively target modifiable risk factors and may facilitate risk stratification. The Frailty Risk Score (FRS) is a chart review‐based approach based on eight symptoms and four laboratory biomarkers. We applied this method in a retrospective study to investigate its utility in predicting post‐transplant lung outcomes. Eighty‐four lung transplant recipients were evaluated, including 51 older (≥ 60) and 33 younger (< 60) patients. Median FRS score was 3.9, with 63 categorized as frail (75%) and 21 as non‐frail (25%), using a previously published cut‐off of ≥3 to define frailty. A high FRS was associated with readmission in the first year after transplantation and with the number of readmissions. There was also an association between FRS score and death (p =.047). FRS may be a viable tool in the assessment of lung transplant candidates. Frail patients may benefit from earlier referral and targeted therapy prior to transplant, as well as close post‐transplant follow‐up. [ABSTRACT FROM AUTHOR]

After kidney transplantation, infection and death are important clinical complications, especially for the growing numbers of older patients with limited resilience to withstand adverse events. Evaluation of changes in gene expression in immune cells can reveal the underlying mechanisms behind vulnerability to infection. A cohort of 60 kidney transplant recipients was evaluated. Gene expression in peripheral blood mononuclear cells 3 months after kidney transplantation was analyzed to compare differences between patients with infection and those who were infection‐free in the first‐year post‐transplant. Pro‐inflammatory genes such as IL1B, CCL4, and TNF were found to be downregulated in post‐transplant PBMC from patients who developed infection. In contrast, genes involved in metabolism, HLA genes, and transcripts involved in type I interferon innate antiviral responses were found to be upregulated. Promoter‐based bioinformatic analyses implicated increased activity of interferon regulatory factors, erythroid nuclear factor (E2), and CCAAT‐enhancer‐binding protein (C/EBP) in patients who developed infections. Differential patterns of gene expression were observed in patients who developed infection after kidney transplantation, with patterns distinct from changes associated with patient age, suggesting possible mechanisms behind vulnerability to infection. Assessment of gene expression in blood may offer an approach for patient risk stratification and monitoring after transplantation. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection continues to negatively affect outcomes for solid organ transplant recipients, despite the advent of strategies for preemptive surveillance and prophylaxis. The impact is especially great for CMV seronegative recipients of donor seropositive organs, who typically lack the ability to control CMV infection at the time of transplantation. Methods: We reviewed episodes of CMV DNAemia in a modern cohort of kidney transplant recipients over a 3‐year period at a high‐volume transplant center to investigate the frequency of DNAemia during antiviral prophylaxis. Results: Despite receipt of antiviral prophylaxis per current guidelines, 75 cases of CMV DNAemia were observed in the first 100 days after transplantation. For high risk patients, median time to DNAemia was 75 days after transplantation, and the majority of patients had experienced dose‐reduction of valganciclovir due to renal insufficiency. Review of CMV seropositive intermediate risk patients demonstrated DNAemia occurring earlier after transplantation compared with high risk patients with a median time of 64 days (P =.029). The impact of valganciclovir dose adjustment was less notable in the intermediate risk group. Conclusions: Guidelines recommend beginning routine surveillance for CMV after the completion of antiviral prophylaxis. Our findings suggest that closer monitoring may be beneficial, especially for high risk patients at risk for DNAemia. Patients requiring dose adjustment of valganciclovir due to renal insufficiency may be at increased risk for CMV DNAemia. Improved methods for CMV prophylaxis and evaluation of immunologic risk for CMV DNAemia and disease are needed to improve patient outcomes after kidney transplantation. [ABSTRACT FROM AUTHOR]

The infectious disease coronavirus disease 2019 (COVID‐19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID‐19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re‐evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID‐19 screening scrutiny and recipient waiting list management in anticipation of COVID‐19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end‐stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020. [ABSTRACT FROM AUTHOR]

Background Transplant Infectious Diseases ( TID) is a rapidly growing subspecialty, which has contributed significantly to improving patient outcomes after transplantation. Obtaining institutional support to implement programs that promote excellence in patient care remains a challenge for many non-surgical transplant-related specialties. Method We surveyed the membership of the American Society of Transplantation Infectious Diseases Community of Practice to assess characteristics of individual transplant programs and delineate current patterns of institutional support of TID, with a goal of facilitating the exchange of innovative funding ideas between transplant programs. Results Of 53 questionnaires returned, 36 programs reported the existence of a dedicated TID service for adults. Of these, the ratio of dedicated TID providers to the number of solid organ transplant patients transplanted annually ranged from 15:1 to 259:1. A total of 21% of responding programs indicated that they received no support from their institution. Respondents from larger programs were more likely to receive some type of programmatic support. Conclusion Given that the presence of expert TID input into patient care can improve outcomes through direct patient management and transplant team education, we suggest that continued support of the unbillable time contributed by TID practitioners is a critical part of ensuring excellent outcomes after transplantation. [ABSTRACT FROM AUTHOR]

Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients. Fifty-six patients received diagnostic procedures, including 46 bronchoscopies, 25 lung biopsies and seven sinus biopsies, with a diagnostic yield for IFI of 12.8%, 35.0% and 83.3%, respectively. In conclusion, chest CT plays an important role in the evaluation of haematological patients with febrile neutropenia and often leads to a change in antimicrobial therapy. Pulmonary nodules are the most common radiological abnormality. Sinus or lung biopsies have a high-diagnostic yield for IFI as compared to bronchoscopy. Patients with IFI may not have sinus/chest symptoms, and thus, clinicians should have a low threshold for performing sinus/chest imaging, and if indicated and safe, a biopsy of the abnormal areas. [ABSTRACT FROM AUTHOR]

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of adenovirus infections after solid organ transplantation. Adenovirus is an important cause of infectious complications in both stem cell transplant and SOT patients, causing a range of clinical syndromes including pneumonitis, colitis, and disseminated disease. The current update of the guidelines highlights that adenovirus surveillance testing should not be performed in asymptomatic recipients. Serial quantitative PCR might play a role in the decision to initiate or assess response to therapy in a symptomatic patient. The initial and most important components of therapy remain supportive care and decrease in immunosuppression. The use of antiviral therapy is not supported by prospective randomized clinical trials. However, intravenous cidofovir is considered the standard practice for treatment of severe, progressive, or disseminated adenovirus disease in most transplant centers. Intravenous immunoglobulin may be beneficial, primarily in a select group of patients with hypogammaglobulinemia. Future approaches to treatment of adenovirus disease may include administration of adenovirus‐specific T‐cell therapy. [ABSTRACT FROM AUTHOR]

Background: Kidney transplant recipients (KTRs) are at risk for reactivation and complicated infection due to Coccidioides. Pre‐transplant serological screening should provide benefit for patients from endemic areas. We evaluated Coccidioides seroprevalence by area of residence in KTRs at a major transplant program in Los Angeles. Methods: We performed cross‐sectional analyses of adult KTRs who underwent transplantation at UCLA between 2007‐2016. Patients with Coccidioides serology by enzyme immunoassay (EIA) before or within 14 days from transplantation were included. Patients were classified as living in highly, established, suspected, or not endemic areas by their residential zip code. Results: Overall prevalence of Coccidioides IgG and IgM were 1.4% and 2.8%, respectively. Of patients with positive serology, 31.4% had isolated IgG and 66.3% isolated IgM. Patients from established and highly endemic areas had IgG seropositivity of 3.7% versus 1.3% for patients living in suspected endemic areas(P < .01). Rates of IgM seropositivity were 3.7% compared to 2.8% respectively (P = .28). No patients from non‐endemic areas had positive screening serology. Conclusions: Pre‐transplant serological screening for Coccidioides is recommended in kidney transplant candidates from endemic areas. We observed high seroprevalence among patients from highly and established endemic areas, for whom universal prophylaxis is recommended. For residents from less well‐established areas of endemicity, serological screening showed benefit in identifying patients at risk. In patients with isolated EIA IgM, performing repeat and confirmatory tests is recommended. Patients from non‐endemic areas had low risk of infection, however, a thorough social history is necessary to evaluate risk. [ABSTRACT FROM AUTHOR]